University of California, Irvine, Department of Biological Sciences, Molecular Biology and Biochemistry

Dr. Donald F. Senear

(Ph.D., University of Washington, 1980)

Interactions of proteins and DNA in transcriptional regulation

  • Faculty Profile

    Publications via PubMed (NIH National Library of Medicine)

  • E-mail: dfsenear@uci.edu

    •     Our goal is to understand the fundamental mechanisms of transcriptional regulation at the level of macromolecular structure, function and interactions. Initiation of transcription, the primary point for control of gene expression, is regulated by the spontaneous assembly of regulatory protein and DNA containing complexes. Specific promoters are metabolically or developmentally regulated through coupling interactions between the site-specific protein-DNA interactions and protein-protein interactions, protein and DNA conformational transitions and allosteric transitions mediated by binding of regulatory ligands. Understanding the chemical basis for these macromolecular interactions provides the foundation to understand biological mechanisms of metabolic regulation, differentiation and development, and carcinogenesis.

        Research is focused on model systems chosen because they embody important general features of both coordinate and differential gene regulation. In our lab or through collaboration we use a variety of biophysical chemical and molecular biological approaches to investigate the interactions, understand their underlying chemical and structural mechanisms and identify regions of the macromolecules responsible for generating the significant forces. These approaches include DNA and inducer binding studies, protein polymerization studies, mutagenesis, pseudo-intrinsic fluorescence  probes to monitor protein and DNA dynamics, computer modeling and crystallography.

    Selected Publications 
    Role of multiple CytR binding sites on cooperativity, competition,
     and induction at the Escherichia coli udp promoter, Gavigan SA, Nguyen T, Nguyen N, Senear DF 
     J Biol Chem 1999 Jun 4;274(23):16010-16019

Activation of gene expression by a ligand-induced conformational change of a protein-DNA complex. 
     Rhee KY, Senear DF, Hatfield GW. 
     J Biol Chem 1998 May 1;273(18):11257-11266.

Linkage between operator binding and dimer to octamer self-assembly of bacteriophage lambda cI repressor.; 
     Rusinova E, Ross JBA, Laue TM, Sowers LC, Senear DF. 
     Biochemistry 1997 Oct 21;36(42):12994-13003.

Allosteric mechanism of induction of CytR-regulated gene expression. Cytr repressor-cytidine interaction.
     Barbier CS, Short SA, Senear DF. 
     J Biol Chem 1997 Jul 4;272(27):16962-16971.

An aromatic stacking interaction between subunits helps mediate DNA sequence specificity: operator site 
     discrimination by phage lambda cI repressor. Huang YT, Rusinova E, Ross JB, Senear DF. 
     J Mol Biol 1997 Mar 28;267(2):403-417.

Multiple specific CytR binding sites at the Escherichia coli deoP2 promoter mediate both cooperative and 
     competitive interactions between CytR and cAMP receptor protein. Perini LT, Doherty EA, Werner E, Senear DF. 
      J Biol Chem 1996 Dec 27;271(52):33242-33255.
        Dr. Senear is part of the UCI Graduate Track in Structural Biology and Molecular Biophysics, and the Track for Gene Expression, within the UCI graduate Program in Molecular Biology, Genetics, and Biochemistry. Applications requests or additional information about the graduate program may be obtained by electronic mail at gp-mbgb@uci.edu or by phone at (949) 824-8145. On-line applications may also be submitted through the Office of Research and Graduate Studies.

    1) Molecular Biology, Genetics, and Biochemistry

    2) Email: gp-mbgb@uci.edu or call (949) 824-8145

    3) Graduate Studies Home Page, with links to On-line applications and the Office of Research and Graduate Studies

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